rs377734902

Variant names:

• chr5-132370251-G-C
• rs377734902
• NM_003060.4:c.279G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-132370251-G-C
• chr5-132370251-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_003060.4(SLC22A5):​c.279G>C​(p.Ser93Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000742 in 1,578,882 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S93S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00072 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00074 (1 hom.)
• Consequence: SLC22A5 NM_003060.4 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:7
• Conservation: PhyloP100: -1.68
• Publications: 3 publications found

Genes affected

SLC22A5 (HGNC:10969): (solute carrier family 22 member 5) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. The encoded protein is a plasma integral membrane protein which functions both as an organic cation transporter and as a sodium-dependent high affinity carnitine transporter. The encoded protein is involved in the active cellular uptake of carnitine. Mutations in this gene are the cause of systemic primary carnitine deficiency (CDSP), an autosomal recessive disorder manifested early in life by hypoketotic hypoglycemia and acute metabolic decompensation, and later in life by skeletal myopathy or cardiomyopathy. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2015]

MIR3936HG (HGNC:40538): (MIR3936 host gene)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 5-132370251-G-C is Benign according to our data. Variant chr5-132370251-G-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 460406.
• BP7: Synonymous conserved (PhyloP=-1.68 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003060.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A5	NM_003060.4	MANE Select	c.279G>C	p.Ser93Ser	synonymous	Exon 1 of 10	NP_003051.1
	SLC22A5	NM_001308122.2		c.279G>C	p.Ser93Ser	synonymous	Exon 1 of 11	NP_001295051.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A5	ENST00000245407.8	TSL:1 MANE Select	c.279G>C	p.Ser93Ser	synonymous	Exon 1 of 10	ENSP00000245407.3
	SLC22A5	ENST00000435065.7	TSL:1	c.279G>C	p.Ser93Ser	synonymous	Exon 1 of 11	ENSP00000402760.2
	SLC22A5	ENST00000448810.6	TSL:1	n.279G>C		non_coding_transcript_exon	Exon 1 of 10	ENSP00000401860.2

Frequencies

GnomAD3 genomes AF: 0.000723 AC: 110 AN: 152206 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.000392

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000600 AC: 109 AN: 181690 AF XY: 0.000655

Gnomad AFR exome AF: 0.000109

Gnomad AMR exome AF: 0.000363

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00101

Gnomad OTH exome AF: 0.000204

GnomAD4 exome AF: 0.000744 AC: 1062 AN: 1426560 Hom.: 1 Cov.: 31 AF XY: 0.000778 AC XY: 550 AN XY: 706612

African (AFR) AF: 0.000184 AC: 6 AN: 32568

American (AMR) AF: 0.000284 AC: 11 AN: 38680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25618

East Asian (EAS) AF: 0.0000267 AC: 1 AN: 37396

South Asian (SAS) AF: 0.000899 AC: 74 AN: 82276

European-Finnish (FIN) AF: 0.0000203 AC: 1 AN: 49256

Middle Eastern (MID) AF: 0.000183 AC: 1 AN: 5466

European-Non Finnish (NFE) AF: 0.000854 AC: 936 AN: 1096180

Other (OTH) AF: 0.000541 AC: 32 AN: 59120

GnomAD4 genome AF: 0.000722 AC: 110 AN: 152322 Hom.: 1 Cov.: 33 AF XY: 0.000738 AC XY: 55 AN XY: 74484

African (AFR) AF: 0.0000962 AC: 4 AN: 41592

American (AMR) AF: 0.000392 AC: 6 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4830

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000882 AC: 60 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000670 Hom.: 0

Bravo AF: 0.000945

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	4	Renal carnitine transport defect (5)
-	-	2	not provided (2)
-	-	1	Decreased circulating carnitine concentration (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.1
DANN	Benign	0.85
PhyloP100		-1.7
PromoterAI		-0.0049	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs377734902; hg19: chr5-131705943;